Cisplatin-DNA adduct repair of transcribed genes is controlled by two circadian programs in mouse tissues

Yang, Yanyan; Adebali, Ogün; Wu, Gang; Selby, Christopher P.; Chiou, Yi Ying; Rashid, Naim U.; Hu, Jinchuan; Hogenesch, John B.; Sancar, Aziz

doi:10.1073/pnas.1804493115

Cited by 75 publications

(79 citation statements)

References 48 publications

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“…Second, our data reveal an interesting aspect of the circadian clock on repair: As reported previously (13), the circadian clock controls excision repair of the TS of clock-controlled genes through its effect on transcription, and the magnitude of this effect is proportional to the transcription rate. In addition, the clock also controls the basal excision repair activity through its control of XPA expression, which peaks at ZT8 -10 (2, 3).…”

Section: Circadian and Transcriptional Control Of Dna Repairsupporting

confidence: 71%

“…In this study, it was not possible to monitor basal repair rhythmicity as done previously. In our prior study, the basal repair rhythmicity was not large, but it was detected among mice which were sampled 2 h after each injection (13). In the present study, with sampling of mice for increasing periods following injection, and also with the transition in repair from TS to NTS with time, significant increases in the NTS and global repair signals were produced to the extent that they dwarfed and rendered undetectable any expected circadian variations in global repair from one ZT to the next.…”

Section: Circadian and Transcriptional Control Of Dna Repairmentioning

confidence: 90%

“…To investigate this possibility, we have been using the XR-seq 2 method (7-9) which allows us to map, across an entire genome, at single nucleotide resolution, where excision repair has occurred among a population of cells. We have applied this method to cells of different organisms (10 -12), and recently we adapted XR-seq to mice, where we found two main circadian programs of repair (13,14). First, basal nucleotide excision repair activity exhibits a single peak at about ZT 8 -10 (ZT ϭ 0 is time of lights on and ZT ϭ 12 is lights off under 12 h light:12 h dark conditions) which is associated with a corresponding rhythmic oscillation of the XPA excision repair factor (2,3).…”

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confidence: 99%

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Long-term, genome-wide kinetic analysis of the effect of the circadian clock and transcription on the repair of cisplatin-DNA adducts in the mouse liver

Yang

Liu

Selby

et al. 2019

Journal of Biological Chemistry

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Edited by Patrick Sung Cisplatin is the most commonly used chemotherapeutic drug for managing solid tumors. However, toxicity and the innate or acquired resistance of cancer cells to the drug limit its usefulness. Cisplatin kills cells by forming cisplatin-DNA adducts, most commonly the Pt-d(GpG) diadduct. We recently showed that, in mice, repair of this adduct 2 h following injection is controlled by two circadian programs. 1) The circadian clock controls transcription of 2000 genes in liver and, via transcription-directed repair, controls repair of the transcribed strand (TS) of these genes in a rhythmic fashion unique to each gene's phase of transcription. 2) The excision repair activity itself is controlled by the circadian clock with a single phase at which the repair of the nontranscribed strand (NTS) and the rest of the genome takes place. Here, we followed the repair kinetic for long periods genome-wide both globally and at single nucleotide resolution by the Excision Repair-sequencing (XR-seq) method to better understand cisplatin DNA damage and repair. We find that transcription-driven repair is nearly complete after 2 days, whereas weeks are required for repair of the NTS and the rest of the genome. TS repair oscillates in rhythmically expressed genes up to 2 days post injection, and in all expressed genes, we see a trend in TS repair with time from the 5 to 3 end. These findings help to understand the circadian-and transcription-dependent and-independent control of repair in response to cisplatin, and should aid in designing cisplatin chemotherapy regimens with improved therapeutic indexes. Circadian rhythmicity of metabolic processes significantly impacts physiology and behavior (1). As a notable example, in mice, excision repair of DNA damage is rhythmic, and daily variations in repair activity are associated with daily variations in sensitivity to UV-induced skin cancer (2, 3). The molecular basis for the circadian clock is a transcription-translation feedback loop in which transcription of clock-controlled genes is activated by BMAL1-CLOCK heterodimers binding to E-box

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Section: Circadian and Transcriptional Control Of Dna Repairsupporting

confidence: 71%

Section: Circadian and Transcriptional Control Of Dna Repairmentioning

confidence: 90%

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confidence: 99%

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Long-term, genome-wide kinetic analysis of the effect of the circadian clock and transcription on the repair of cisplatin-DNA adducts in the mouse liver

Yang

Liu

Selby

et al. 2019

Journal of Biological Chemistry

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“…Cisplatin interacts with DNA mainly in the form of Pt-d(GpG) diadducts, which inhibit cell proliferation and activate the DNA damage response (DDR). 5,6 The DNA damage checkpoint is a complex signal transduction pathway that includes ATM, ATR, Chk1, Chk2, the MRN complex, and other checkpoint proteins. 7,8 Once the DDR is activated, cell cycle arrest is initiated to repair DNA or induce apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of KLF5 promotes cisplatin‐induced cell apoptosis via regulating DNA damage checkpoint proteins in non‐small cell lung cancer

et al. 2019

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Background Previous research has revealed that Krüppel‐like factor 5 ( KLF5 ) may affect DNA damage repair pathways; however, the associated molecular mechanisms are unclear. Methods The expression of KLF5 was studied by immunohistochemical staining in paired tumour and normal tissues from 90 patients with ESCC. We studied the effects of KLF5 knockdown on cell proliferation and apoptosis with or without cisplatin treatment in A549 and H1299 cell lines. Moreover, we examined the effect of KLF5 on the DNA damage response. Results KLF5 was significantly overexpressed in non‐small cell lung cancer (NSCLC) tissues, and high KLF5 expression predicted poor prognosis for NSCLC patients. The inhibition of KLF5 markedly augmented cisplatin‐induced cell apoptosis. In addition, we observed that KLF5 knockdown could decrease DNA repair potential by inhibiting H2AX S139 phosphorylation in response to cisplatin. Moreover, silencing of KLF5 in NSCLC cell lines inhibited the phosphorylation of checkpoint kinases Chk1 S345 and Chk2 T68. KLF5 knockdown permits cells with broken or damaged DNA strands to enter mitosis by inhibiting the activation of H2AX, Chk1 and Chk2, resulting in mitotic catastrophe. Conclusion KLF5 plays a significant role in the DNA damage response by regulating DNA damage checkpoint proteins. Inhibition of KLF5 may be a potential therapeutic target for NSCLC patients with cisplatin resistance.

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“…Accumulating evidence suggests that DNA adduct repair including the excision repair system is under circadian control (Yang et al., ). Excision repair, a key participant in the repair of alcohol‐associated DNA damage (Balbo and Brooks, ; Brooks, ; Matsuda et al., ; Slyskova et al., ), shows a diurnal variation in several nonintestinal tissues (i.e., liver, brain, and skin; Gaddameedhi et al., ; Kang et al., , ).…”

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confidence: 99%

Alcohol Effects on Colon Epithelium are Time‐Dependent

Bishehsari

Zhang

Voigt

et al. 2019

Alcoholism Clin & Exp Res

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Background: Alcohol intake increases the risk of developing colon cancer. Circadian disruption promotes alcohol's effect on colon carcinogenesis through unknown mechanisms. Alcohol's metabolites induce DNA damage, an early step in carcinogenesis. We assessed the effect of time of alcohol consumption on markers of tissue damage in the colonic epithelium.Methods: Mice were treated by alcohol or phosphate-buffered saline (PBS), at 4-hour intervals for 3 days, and their colons were analyzed for (i) proliferation (Ki67) and antiapoptosis (Bcl-2) markers, (ii) DNA damage (c-H2AX), and (iii) the major acetaldehyde (AcH)-DNA adduct, N 2 -ethylidene-dG. To model circadian disruption, mice were shifted once weekly for 12 h and then were sacrificed at 4hour intervals. Samples of mice with a dysfunctional molecular clock were analyzed. The dynamics of DNA damage repair from AcH treatment as well as role of xeroderma pigmentosum, complementation group A (XPA) in their repair were studied in vitro.Results: Proliferation and survival of colonic epithelium have daily rhythmicity. Alcohol induced colonic epithelium proliferation in a time-dependent manner, with a stronger effect during the light/rest period. Alcohol-associated DNA damage also occurred more when alcohol was given at light. Levels of DNA adduct did not vary by time, suggesting rather lower repair efficiency during the light versus dark. XPA gene expression, a key excision repair gene, was time-dependent, peaking at the beginning of the dark. XPA knockout colon epithelial cells were inefficient in repair of the DNA damage induced by alcohol's metabolite.Conclusions: Time of day of alcohol intake may be an important determinant of colon tissue damage and carcinogenicity.

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Cisplatin-DNA adduct repair of transcribed genes is controlled by two circadian programs in mouse tissues

Cited by 75 publications

References 48 publications

Long-term, genome-wide kinetic analysis of the effect of the circadian clock and transcription on the repair of cisplatin-DNA adducts in the mouse liver

Long-term, genome-wide kinetic analysis of the effect of the circadian clock and transcription on the repair of cisplatin-DNA adducts in the mouse liver

Knockdown of KLF5 promotes cisplatin‐induced cell apoptosis via regulating DNA damage checkpoint proteins in non‐small cell lung cancer

Alcohol Effects on Colon Epithelium are Time‐Dependent

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